Organotin arsonate derivatives



United States Patent I 2,762,821 ORGANOTIN ARSONATE DERIVATIVES ArthurW. Walde, Harold E. Van Essen, Jr., and Thomas W. Zbornik, Charles'City, Iowa, assignors to Dr. Salshurys Laboratories, Charles City,Iowa, a corporation of Iowa v No Drawing. Application July 6, 1953,

Serial No. 366,398

'14 Claims. Cl. 260429.7)

uable remedies in the prophylactic control and suppression of variousprotozoal infections such as cpccidiosis, heitamitiasis andhistomoniasis in poultry.' Theiy are also potent anthelmintics in thetreatment of avian tapeworm infections, and they have shown considerableusefulness as insecticides and chloride scavengers.

I their broadest aspect our new compounds may be represented by thegeneralempiric formula i R(n)'SH'[OH(m)Z]3-n-)- m wherein R may be asubstituted or unsubstituted alkyl, aryl, aralkyl or heterocyclicradical, Z represents the arsonic acid group n is either 2 vor 3, m iseither 0 or 1, n-m is not greater than 2, and wherein the oxygen in thebracketed portion is attached to the arsenic atom in Z and is linked tothe tin atom when m is O, and to the hydrogen atom when m is 1.

The compounds covered by the foregoing formula include three classes ofarsonates defined by the following structural configurations, in whichthe letter R designates the organic moiety attached to the tin atom, andthe'letter R denotes similar substituents in the arsonic group.

I. Tri-organo tin monoarsonates i when n=2, and m=1;

III. Di-organo tin monoarsonates As already indicated, the substituentsR and R may include a wide variety of radicals. They may, for instance,be represented by any substituted or unsubstituted alkyl group derivedfrom the class of paraifines or saturated hydrocarbons. Examples of suchresidues are "ice 2 methyl, ethyl, propyl, butyl, lauryl, amyhhex'yl,benzyl, and so forth. The grouflmay'consist of straight'chain radicalswtih progressive carbon linkages, and it may also includeisomericderivatives of chain and side; chain struc'- tures, such asZ-niethyl' butyl and iso'propyl. The 'alkyl group may further besubstituted by'various other radi-' cals such as hydroxyjhalogen, nitroor aniino; or it may contain an oxygen bridge as inimethoxye thyl,ethoxyethyl, butoxyethyl, but'oxypropyl, butox'ybutyl, and similarstructures. i i

R and'R' may also stand for unsaturated derivatives of the paraffinicseries which are cornmonly known as 211- kenes and alkynes. Bothstraight 'chainand branched chain substituents can beused withinthisseries Eicamples are allyl, l-buten'yl, '2-butenyl,' l-p'entenyl,crotyl, cinnamyl and equivalent groups. Asa further variation R and Rmay be formed by alicyclic radicals of aliphatic nature such ascyclohexyl'and'cyclopropyl.

Among the aromatic structure's'R and R may be represented by anysubstituted or unsubstituted members of the benzene class, 'such'asphenyLtolyl, 'Xyl'yl and cymyl. Each of the residues may again besubstituted both in the nucleus and in "the sideth'ain-by such groups as'nitro; amino, halogen, hydroxyl andithe like. In additionto the phenylring'radicals, the next higher homologuesmay constitute theorganidmoietfof R and R as 'illiistrate l by fiaphthyl, antliiacyl "and"their Variedlyisubstituted derivatives. Exa'i'nplcsof heter'ocyclicradicals are furyl', thienyl, thenyl, pyridil, pyrimid'yl,pyrazylf'quiiioxalyl, etc. The several R and R portions'in the moleculeof our new organo tin arsonates may be either of identical structure orthey may be formed bysdiflferent radicals; Thus, for instance, R may lstandl for butyl and crotyl, while R' is represented a phenyl or vasubstituted phenylgrou pf H r l Specific illustrations ofour nevicompounds included in the above defined threeiclasses' of organo tinarsonatesare: 1 1

Tributyl tin benzene arsonate Tributyl tin 4-nitrobenzene arsonateTributyl tin 3- nitro-4-ihyd'roxybenzene arsonate Tributyl tin'3-nitro-4-aminobenzene arsonate Tributyl tin 4-chlorobenzene arsonateTributyl tin 2-chlorobenzene arsonate Tributyl tin 4-aminobenzenearsonate Tributyl tin 4-hydroxybenzene arsonate Triphenyl tin benzenearsonate Triphenyl tin 4-nitrobenzene arsonate Triphenyl. tin3v-nitro-4-hydroxybenzene arsonate Triphenyl itn3-nitro-4i-aminob'enzene arsonate I Triphenyl tin4-chlorobenzene.arsonate Triphenyl tin 2-chlorobenzene arsonateTriphenyl tin 4-aminobenzene arsonate Triphenyl tin4-hydroxybenzene.,Tarsonate Tribenzyl tin benzene arsonate Tribenzyl tin4-nitrobenzene arsonate Tribenzyl tin 3 nitro-4;hydroxybenzene arsonateTribenzyl tin 3-nitrof4 aminobenzene arsonate Tribenzyl tin4-chlorobenzene arsonate Tribenzyl tin ZTQhQ Q 'QbQIlZCHE arsonate T benyl n Aram Q benZm ar n t Tribenzyl tin fl-h'ydr Xybenzene arsonateTri-para-tolyl tin ,na thylfarsona'te' T jy'c bhexy tin e1; a fdnatDibu'tyl" lau'ryl tin ,4;hydrbx'ybe'nzene arsonate iD a yl .b zy' t.fiknitta-Aami b hzen emanat Dibutyl tin (ii-(benzene arsonate) Dibutyltin di-(4-nitrobenzene arsonate) Dibutyl tin di-(3-nitro4-hydroxybenzenearsonate) Dibutyl tin di-(3-nitro-4-aminobenzene arsonate) Dibutyl tindi-(4-chlorobenzene arsonate) Dibutyl tin di-(2-chlorobenzene arsonate)Dibutyl tin di-(4-aminobenzene arsonate) Dibutyl tindi-(4-hydroxybenzene arsonate) Diphenyl tin di-(benzene arsonate)Diphenyl tin di-(4-nitrobenzene arsonate) Diphenyl' tindi-(3-nitro-4-hydroxybenzene arsonate) Diphenyl tindi-(.3-nitro-4-aminobenzene arsonate) Diphenyl tin di-(4-chlorobenzenearsonate) Diphenyl tin di-(Z-chlordbenzene arsonate) Diphenyl tindi-(4-aminobenzene arsonate) Diphenyl tin di-(4-hydroxybenzene arsonate)Dibenzyl tin di-(benzene arsonate) Dibenzyl tin di-(4-nitrobenzenearsonate) Dibenzyl tin di-(3-nitro-4-hydroxybenzene arsonate) Dibenzyltin di-(3-nitro-4-aminobenzene arsonate) Dibenzyl tindi-(4-chlorobenzene arsonate) Dibenzyl tin di-(Z-chlorobenzene arsonate)Dibenzyl tin di-(4-aminobenzene arsonate) Dibenzyl tindi-(4-hydroxybenzene arsonate) Diphenyl tin dibutyl arsonateDi-(para-bromophenyl) tin dibutyl arsonate Diethoxy ethyl tin di-(propylarsonate) Benzyl-butyl-phenyl tin di-(4-nitrobenzene arsonate) l-Butenyll-pentenyl tin di-(methyl arsonate) l-Dinaphthyl tindi-(3-nitro-4-hydroxybenzene arsonate) Benzyl paratolyl tindi-(4-hydroxybenzene arsonate) III Dibutyl tin benzene arsonate Dibutyltin 4-nitrobenzene arsonate Dibutyl tin 3-nitro-4-hydroxybenzenearsonate Dibutyl tin 3-nitro-4-aminobenzene arsonate Dibutyl tin 4chlorobenzene arsonate Dibutyl tin 2-chlorobenzene arsonate Dibutyl tin4-aminobenzene arsonate Dibutyl tin 4-hydroxybenzene arsonate Diphenyltin benzene arsonate Diphenyl tin 4-nitr0benzene arsonate Diphenyl tin3-nitro-4-hydroxybenzene arsonate Diphenyl tin 3-nitro-4-aminobenzenearsonate Diphenyl tin 4-chlorobenzene arsonate Diphenyl tinZ-chlorobenzene arsonate Diphenyl tin 4-aminobenzene arsonate Diphenyltin 4-hydroxybenzene arsonate Dibenzyl tin benzene arsonate Dibenzyl tin4-nitrobenzene arsonate Dibenzyl tin 3-nitro-4-hydroxybenzene arsonateDibenzyl tin 3-nitro-4-aminobenzene arsonate Dibenzyl tin4-chlorobenzene arsonate Dibenzyl tin 2-chlorobenzene arsonate Dibenzyltin 4-aminobenzene arsonate Dibenzyl tin 4-hydroxybenzene arsonateDibutyl tin 3-nitrobenzene arsonate Diphenyl tin butyl arsonateDi-(para-iodophenyl) tin heptyl arsonate Cyclohexyl phenyl tin4-nitrobenzene arsonate Benzyl amyl tin butyl arsonate Diortho anisyltin 4-aminobenzene arsonate The physical properties of the compounds,particularly their melting points and solubilities in organic solventsvary with their structural configurations. For the most part they arecrystalline solids with decomposition points or melting points above 150C. The members of class II comprising two arsonic acid units aregenerally soluble in normal butyl alcohol while the monoarsonates ofseries I and 111 show no solubility in organic solvents. They aretherefore used in various organic or inorganic media in suspended ordispersed form, stabilized by suitable surface active agents.

structurally, the substances may be considered as organotia salts ofarsonic acid which has the formula given on the following page.

H HO-As-R wherein two electropositive hydrogen atoms are available forsalt formation with the electronegative portions of an organotincompound. In classes I and II only one of the arsonic hydrogens hasentered into reaction, while in series III both of the acidic functionshave come into union with the tin moiety by the formation of a doubleoxygen bridge. corroboration of these structural concepts is supplied bythe assay values for arsenic and tin and also by the nature and amountsof the by-products eliminated during the condensation process.

The new substances are generally prepared by subjecting organotincompounds carrying readily reactive polar groups to the action of anarsonic acid at elevated temperatures, whereby the polar radical of theorganotin molecule combines with one or more hydrogen ions of thearsonic acid and is replaced by the electronegative arsonic acidportion. Organotin compounds capable of this reaction are the acetates,butyrates, oxides, hydroxides and many other equivalent structures withcomparatively labile electronegative functions. If, for instance, abutyl tin oxide is reacted with an arsonic acid, the oxygen atom of thetin compound will unite with the two hydroxylic hydrogens of the acidwith formation of water which can be collected and assayed by the methodof Dean and Stark. In the case of anacetate, acetic acid will be evolvedin the corresponding manner and its amount can be determined by theweight loss of the reaction mixture. It is thus possible to check thecourse of the reaction for evidence of how many mols of the reactingpartners have undergone condensation.

The process can be carried out with or without solvents; when solventsare used, suitable selections are benzene, toluene, xylene and aceticacid.

The temperature at which the reaction is effected lies at least at steambath temperature or about at 200 F.; however in certain cases involvingsluggish molecules a higher thermal excitation may be required. Thecondensation is ordinarily completed within about one to two hours.

It will be observed that the reaction between the organotin compoundsand the arsonic acid proceeds in strict stoichiometric proportions.Thus, if 1 mol of a bipolar tin compounds is condensed with 2 mols of anarsonic acid, only one hydroxylic hydrogen of each will participate inthe reaction to form a diarsonate If, on the other hand, only 1 mol ofarsonic acid is used, both hydroxylic hydrogen ions will be activatedand a monoarsonate will be obtained Example 1.-Di-n-butyl tindi-(4-n1'tr0benzene arsonate) 70.2 grams (0.2 mol) of the liquidcompound di-n-butyl tin diacetate were thoroughly mixed with 98.8 grams(0.4 mol) of 4-nitr0benzenearsonic acid. After solidification themixture was-heated for one? hour on the steam bath. During thecondensation acetic acid vapors evolved and the weight loss of thereaction mixture was 23.5 grams corresponding to'0.4 'mol of acetic acid(theory 24.01 grams). The product was-ground to 100% minus 20 mesh anddried at 200 F. to remove the last traces of acetic acid. The yield was141 grams or 99.8% of the theory. The crude material evolved a gas at190192 C. When recrystallized from n-butyl alcohol, it evolved agas at165172 C. The temperature at which;gas evolution begins depends in somemeasure on the rate of heating the sample in melting point tube. The gasevolved is water. The compound decomposed at 260 C. When subjected toanalysis, the product was found to contain 15.71% of Sn and 19.87% of Aswhich indicates the formula requiring a theoretical content of 16.37% Snand of 20.7% As. I

Example 2.Di-n-bu'tyl tin di-(3-riitr0-4-amin0benzene arsonate) 70.2grams (0.2 mol) of vdi-n-butyl tin diacetate were treated with 104.8(0.4 mol) of 3-'nitro-4-aminobenzerre arsonic acid as outlined in theforegoing example. During the reaction approximately 23.7 gramscorresponding to 0.4 mol or two equivalents .of acetic acid wereevolved.

The resulting product was of a bright yellow color and was obtained in ayield of 141 grams or 99% of the theory.

The product evolved a gas at l 891-93 C. and decomposed at 260 C. Theanalysis gave a value of 16.34% for Sn and 20.2% for As, calling forthe'fonfnula (C4H9)2'Sn- [OAs(O) (OH)C0H3(NH2) (NO2)]2 which requires atheoretical content of 15.72% Sn and 19.83% As.

Example 3.Di-n-butyl tin di-(3-nitr0-4-hydr0xybenzene arsonate) 70.2grams (0.2 mol) of di-n-butyl tin diacetate were mixed with 105.2 grams(0.4 mol) of 3enitro-4-hydroxybenzenearsonic acid. Followingtreatment'in themanner of the previous examples adrycrop of 148 grams or100%-.0f the theory was collected. .ThE'PIOdHCtIEVOlVCd gas at 168-171.C., and. decomposedat 190 C. Upon recrystallizationit evolves a gas at164-170? C. The analysis of the product yielded 15.05% Sn and 20.4% As,thereby supporting the formula '(C4H9)2"Sn- [OAs(O)'(QH)--CsHs(OH)(NO2)12 whichicorresponds to a theoretical value of 15.67%,.Sn and.19L79% ,As.

Example 4.Di-n-butyl tin 'di- (4-nitr0benze ne arson'ate) 20.7, grams(0.0833 mol) of di-n-butyl an oxide were mixed. with 41.2grams (0.167mol) of 4-nitrobenzene arsonic. acid. 400 cc. of toluene were added as asolvent and the mixture was refluxed for approximately two hours.

A stoichiometrical amount of 1.5 ml.=0.0833 molof water was collected inthe Dean and 'Sta'rk. tube, indicating that two arsonic acid radicalshad combinedwith the dini-butyl tin portion. When no more waterevolvedfrorn the mixture, the solution was cooled and the toluene wasdecanted off. The residuewas dried in the air and thereafter ground andscreened. The yield was 60.4 grams. The. material evolved gas at 192 C.and completely decomposed at 250 C. The assay showed a Sn content of15.89% and an As content of 19.84% which closely responds to the formula(C4H9)2SI1'[O--AS(O) (OH)CeH4(NO2)]z requiringatheoretical amount of16.27% Sn and 20.66%

Example 5 .Diphenyl tin dibutyl arsonate) 24.0 grams (0.0833 mol) ofdiphenyl tin oxide were reacted with 30.4 .grams (0.167 mol) of butylarsonic acid as described in Example 4. The reaction was completed after1.5 nil. of water corresponding to 0.0833 mol was collected in the Deanand Stark tube. After drying a yield of 52.5 grams of the compound wasobtained, which decomposed with melting at about 296 C. and showed a Sncontent of 19.25% and an As content of 23.12%, thereby answering theconfiguration (CsH5)2-.Sn- [OAs(O) (OH)--C4H9]2 which requires atheoretical amount of 18.69% Sn and 23.59% As.

.Exqmple 6. Di-n-butyl tin 4-nitr0benzene arsanate 41.5 grams (0.167mol) of di-n-butyl tin 'oxide'were dissolved in toluene and heated atapproximately 115 C. with 41.2 grams (0.167 mol) of 4-nitrobenzenearsonic -acid,'until the stoichiomt'ric amount of 3 ml. equal to0.167'mol of water was removed. After grinding, drying and'scr'eeningayield (7951 grams was obtained. The productdecomposed,at'-'249 C. and upon analysis showed a content of"24.2%Sn-and 15.2% As, indicating the clmjz-snoz Adm-061140102) which callsfor-theoretical values'of 24.84% of Sn and 15.67% of As.

Example 7.'Di-n-bmyl tin Q 3-nitra-4-hydr0xybenzene arsonate(CiHa)z-Sri- (O2) 'As(O)-CHa(OH) (N02) which requires a theoreticalcontent of 24.03% Sn and of 15.16% As.

Example 8.-Din-bulyl tin 4-nitrobenzene arsonate "70.2 grams (0.2 mol)of di-n-butyl tin diacetate were treated with 49.4 grams (0.2 mol) of4-nitrobenzene arsonic acid as in the foregoing example. The weight lossof themixture during the condensation was 24.01 grams corresponding to0.4 mol of acetic acid. A crop of 95.6

gramsor of the theory of'the new product was collected which melted at256 C. with decomposition. The analysis showed 25.21% Sn and 16.2% Ascorresponding to the formula which requires a theoretical content of24.83% of Sn and 15.67% of As. i

Example 9.Di-n-butyl tin 3-nitr0-4-amin0benzene arsonate 70.2 grams (0.2mol) of di-n-butyl tin diacetate were reacted with 52.4 grams (0.2 mol)of 3-nitro-4-aminobenzene arsonic acid until constant weight Wasattained.

The weight loss was 24.02 grams corresponding to the stoichiometricrequirement of 0.4 mol of acetic acid. The yield was 98.6 grams or 100%of the theory and the material decomposed at 262 C. The content of Snwas found to be 24.96% and that of As 14.59%, indicating the formationof (C4H9)2-Sn- (O2) -As(O)-Csm(NO2) (NHz) which theoretically calls for24.07% Sn and 15.2% As.

Example 10.Di-n-butyl tin 4-aminobenzene arsonate which calls for atheoretical value of 26.5% for Sn and of 16.72% for As.

Example 11.Diphenyl tin n-butyl arsonate 2.89 grams (0.01 mol) ofdiphenyl tin oxide and 1.82 grams (0.01 mol) of n-butyl arsonic acidwere mixed with 1.15 ml. of acetic acid. The mixture was heated in anevaporating dish on a hot plate for about 2 hours until a solid mass hadformed. A yield of 3.9 grams=86.4% of the theory was obtained. Theproduct melted at 297 C. with decomposition. The material assayed 27.1%Sn and 16.02% As, answering the formula which calls for theoreticalvalues of 26.28% Sn and 16.7% As.

Example 12.Triphenyl tin 4-nitr0benzene arsonate 6.10 grams (0.0166 mol)of triphenyl tin oxide were placed in a small conical flask with 4.11grams (0.0166 mol) of 4-nitrobenzene arsonic acid. The flask wasconnected with a Dean and Strark apparatus, and the mixture was heatedat 150 C. until all the water of reaction was distilled over. An amountof 0.2 ml. of water, corresponding to one equivalent or 0.0166 mol, wascollected. The yield of product obtained was 9.7 grams or 98% of thetheory. The product melted with decomposition at 272 C. Analysis showeda Sn content of 20.7% and an As content of 12.07%, corresponding to theformula (CsH5)3'Sn- O-As(O)(OH)CsH4(NO2) which requires in theory avalue of 19.92% Sn and of Although the invention has been described 1nthe foregoing examples by way of specific illustrations, it will 5 beappreciated that these examples are not limiting in scope butthat theyare subject to manifold modifications, especially in respect of thestarting materials which oifer a wide variety of selections. It isfurther understood that the structural configurations as given for therecited products are merely based upon reasonable expectations inconformity with current concepts prevailing in chemistry and that it isintended to protect the compounds characterized by their atomic ratiosas obtained in accordance with the foregoing description and theappended claims, despite the possibility that the structuralconfigformed condensate from the mixture.

urations may be later revised in regard to their formulation in thelight of newly acquired knowledge.

What we claim is:

1. Organo tin arsonic acid compounds selected from the group consistingof triorgano tin monoarsonates of the general formula R1 R; SnOl ls-R R;OH diorgano tin monoarsonates of the general formula Sn lS R. .4 0

and diorgano tin diarsonates of the general formula /Sn OH R, L

wherein R1, R2, R3 and R4 are members selected from the group consistingof alkyl, alkenyl, alkynyl, a benzene, naphthyl and anthracyl radicals.

2. Triorganotin arsonates of the general configuration R R SnO1 ls-R ROH wherein R R R and R are selected from the group consisting of alkyl,alkenyl, a benzene, naphthyl and anthracyl radicals.

3. Diorganotin diarsonates of the general formula wherein R R R and Rare selected from the group consisting of alkyl, alkenyl, a benzene,naphthyl and anthracyl radicals. V I

4. Diorganotin monoarsonates of the general formula where R R and R areselected from the group consisting of alkyl, alkenyl, a benzene,naphthyl and anthracyl radicals. p

5. Dibutyl tin di-(4-nitrobenzene arsonate). Y

6. Dibutyl tin di-(3-nitro-4-hydroxybenzene arsonate):

7. Diphenyl tin di-(4-aminobenzene arsonate). Y

8. Dibenzyl tin di-(3-nitro-4-aminobenzene arsonate).

9. Dibutyl tin 4-hydroxybenzene arsonate.

10. A process for preparing organotin arsonates as defined in claim 1comprising the steps of causing an organotin compound carrying readilyreactive electronegative groups to react, at least at steam bathtemperature, with an arsonic acid in substantially stoichiometricamounts ranging from one to two equivalents in proportion to saidelectronegative groups and removing the 11. A process for preparingorganotin arsonates as defined in'claim 1 comprising the'steps ofcausing an organotin compound selected from the group of organetinoxides and low-molecular weight aliphatic carboxylates to react, atleast at steam bath temperature, with an arsonic acid in substantiallystoichiometric amounts ranging from one to two equivalents in proportionto said tin compound and removing the formed volatile product ofreaction.

12. A process for preparing triorganotin arsonates as defined in claim 2comprising the steps of causing 1 mol of a triorganotin hydroxide toreact at about 150 C. with 1 mol of an arsonie acid and removing theformed water of reaction.

13. A process for preparing a diorganotin monoarsonate as defined inclaim 4 comprising the steps of causing 1 mol of a diorganotin oxide toreact, at least at steam bath temperature, with 1 mol of an arsonic acidand removing the formed water of reaction.

14. A process for preparing diorganotin diarsonates References Cited inthe file of this patent UNITED STATES PATENTS 2,560,034 Eberly July 10,1951 2,597,920 Carroll May 27, 1952 2,630,436 Church Mar. 3, 1953 OTHERREFERENCES Rochow et al.: J. Am. Chem. Soc., vol. 75, pp. 3099- 3101,260/429 TIN (received Feb. 20, 1953).

1. ORGANO TIN ARSONIC ACID COMPOUNDS SELECTED FROM THE GROUP CONSISTING OF TRIORGANO TIN MONOARSONATES OF THE GENERAL FORMULA 